Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.

Aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.

4 mg/kg as an intravenous infusion over 1 hour every 2 weeks. Do not administer as an intravenous (IV) push or bolus.

Preparation for Administration: Inspect vials visually prior to use. Aflibercept is a clear, colorless to pale yellow solution. Do not use vial if the solution is discolored or cloudy or if the solution contains particles. Do not re-enter the vial after the initial puncture. Discard any unused portion left in the vial. Withdraw the prescribed dose of Aflibercept and dilute in 0.9% sodium chloride solution, 5% dextrose solution for injection, to achieve a final concentration of 0.6–8 mg/mL.

Use polyvinyl chloride (PVC) infusion bags containing bis (2-ethylhexyl) phthalate (DEHP) or polyolefin infusion bags. Store diluted Aflibercept at 2°–8°C for up to 24 hours, or at controlled room temperature 20°–25°C for up to 8 hours. Discard any unused portion left in the infusion bag.

Administration: Administer the diluted Aflibercept solution as an intravenous infusion over 1 hour through a 0.2 micron polyethersulfone filter. Do not use filters made of polyvinylidene fluoride (PVDF) or nylon. Do not administer as an intravenous (IV) push or bolus. Do not combine Aflibercept with other drugs in the same infusion bag or intravenous line.

Most common adverse reactions (all grades, ≥20% incidence and at least 2% greater incidence for the Aflibercept/FOLFIRI regimen) were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache

Pregnancy & Lactation

Pregnancy category C. There are no adequate and well-controlled studies with Aflibercept in pregnant women. Aflibercept was embryotoxic and teratogenic in rabbits at exposure levels lower than human exposures at the recommended dose, with increased incidences of external, visceral, and skeletal fetal malformations. Aflibercept should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether Aflibercept is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Aflibercept, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Precautions & Warnings

Adverse reactions, sometimes severe and life-threatening or fatal, have been seen in clinical trials with Aflibercept, including:

• Fistula Formation: Discontinue Aflibercept if fistula occurs.
• Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend Aflibercept if hypertension is not controlled. Discontinue Aflibercept if hypertensive crisis develops.
• Arterial Thromboembolic Events (ATE) (e.g., transient ischemic attacks, cerebrovascular accident, angina pectoris): Discontinue Aflibercept if ATE develops.
• Proteinuria: Monitor urine protein. Suspend Aflibercept when proteinuria ≥ 2 grams per 24 hours. Discontinue Aflibercept if nephrotic syndrome or thrombotic microangiopathy (TMA) develops.
• Neutropenia and Neutropenic Complications: Delay administration of Aflibercept/FOLFIRI until neutrophil count is ≥ 1.5 × 109/L.
• Diarrhea and Dehydration: Incidence of severe diarrhea and dehydration is increased. Monitor elderly patients more closely.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue Aflibercept.